Stereospecific dextrorphan tolerance in rats

1 Levorphanol was 20 times more potent than dextrorphan in decreasing food-reinforced fixed ratio 15 responding in male Sprague Dawley rats. 2 Chronic dextrorphan (100 mg/kg, i.p.; every 8 h) resulted in the development of dextrorphan tolerance. The dextrorphan dose-effect curve was shifted to the right three fold. 3 In contrast to dextrorphan, nontolerance developed to the effects of levorphanol. 4 These data support the hypothesis that (+)-isomers of opioids produce pharmacologically distinct CNS effects.